This application is for a Program Project grant to support the research program of the Division of Clinical Research. It includes a series of integrated projects on the general theme of susceptibility and response of humans to oncogenic agents. We now have substantial evidence that the hepatitis B virus (HBV) is etiologically associated with primary hepatocellular carcinoma (PHC, hepatoma). We propose to continue studying the properties of HBV and the characteristics of humans infected with it, in order to specify those aspects of host-virus interaction which lead to the development of PHC. Additional knowledge about HBV may permit us to identify other agents with similar properties which are involved in the etiology and pathogenesis of other cancers. HBsAg appears to interact with genetically determined attributes of humans, and the genetic constitution of the human host may determine the nature of his response. There is also a striking maternal effect. Therefore, a study of HBV, and the hypothesized related agents, requires a concurrent study of host reactions. The program includes studies on the epidemiology, immunology and genetics of PHC, HBsAg and alpha-fetoprotein; the parents of patients with leukemia compared to parents of normal children; a series of studies on maternal effects of HBsAg; chemical, biological and immunologic characteristics of HBV; and the investigation of "new" precipitins found in the serum of transfused patients. In addition, there is an investigation of the characteristics of agents related to the tubercle vacillus (but not BCG) which may be of practical value in the immunotherapy of cancer. BIBLIOGRAPHIC REFERENCES: Wills, W., Saimot, G., Brochard, C., Blumberg, B.S., London, W.T., Dechene, R. and Millman, I. Hepatitis B surface antigen (Australia antigen) in mosquitoes collected in Senegal, West Africa. Am. J. Trop. Med. Hyg. 25:186-190, 1976. Hesser, J.E., Blumberg, B.S. and Drew, J.S. Hepatitis B surface antigen, fertility and sex ratio: Implications for health planning. Human Biol. 48:73-81, 1976.